CN114438523A - Green and efficient electrochemical synthesis method of benzothiophene compound - Google Patents
Green and efficient electrochemical synthesis method of benzothiophene compound Download PDFInfo
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Abstract
The invention discloses a green and efficient electrochemical synthesis method of benzothiophene compounds, which comprises the steps of adding o-methylthio phenylboronic acid, phenylacetylene compounds and electrolyte into a reaction solvent, inserting an electrode, and stirring for reaction under constant current to obtain benzothiophene compounds; wherein R is selected from H, C1-C3 alkyl or halogen. According to the invention, the benzothiophene is obtained by performing free radical addition ring-forming synthesis under the participation of a transition metal-free catalyst and an exogenous strong oxidant by utilizing green electrochemical oxidation, the operation is simple, the cost is low, and the reaction is green and efficient, so that good guidance is provided for the development and application of the structure of the benzothiophene-containing medicament.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a green and efficient electrochemical synthesis method of benzothiophene compounds.
Background
Benzothiophenes are important structural elements of drugs, natural products, dyes and functional materials. In particular, they are widely found in natural products and synthetic drugs, and have various pharmacological actions such as antimicrobial agents, anticancer agents, anti-inflammatory agents, antioxidants, antituberculotic agents, antidiabetic agents, anticonvulsants, and the like. Because of the important value of the compound, the synthesis research of the compound is always the research focus of organic synthesis, in recent years, the synthesis of benzothiophene compounds mostly depends on the assistance of a transition metal catalyst, but the application of the method in the pharmaceutical industry is limited due to the problem of metal residue.
In the last few years, electrochemistry has become a hot topic in the field of organic synthesis due to its environmental friendliness and economy. Emerging electrochemical synthesis uses sustainable and renewable current as the driving force for chemical reactions, and is a green substitute for chemical redox agents. In the electrochemical reaction system, the redox reactivity of a specific substrate can be precisely controlled by slightly adjusting the applied electromotive force. With the increasing attention to electrochemistry, the method is widely applied to classical oxidative coupling and free radical cascade reaction, and the development of a plurality of environment-friendly heterocyclic construction methods is promoted. Therefore, the method for synthesizing the benzothiophene compound by using an economic, green and sustainable electrochemical method has important research significance.
Disclosure of Invention
The purpose of the invention is as follows: in order to solve the problems of high cost, residual transition metal, poor selectivity, difficulty in industrial amplification and the like in the prior art, the invention provides a green and efficient electrochemical synthesis method of benzothiophene compounds.
The technical scheme is as follows: in order to solve the problems, the technical scheme adopted by the invention is as follows:
a green and efficient electrochemical synthesis method of benzothiophenes comprises the steps of adding o-methylthio phenylboronic acid, phenylacetylene compounds and electrolyte into a reaction solvent, inserting an electrode, and stirring under constant current to react to obtain benzothiophenes;
wherein R is selected from H, C1-C3 alkyl or halogen.
Preferably, R is selected from H, CH3、CH2CH3Or Cl.
Preferably, the molar ratio of the reactant o-methylthio phenylboronic acid to the phenylacetylene compound is 1: 1-1: 3, and the more preferable ratio is 1: 2; the molar ratio of the electrolyte to the reactant o-methylthio phenylboronic acid is 1: 1-1: 4, and the more preferable ratio is 1: 2.
Preferably, the electrolyte is one or more of tetrabutylammonium fluoride, tetrabutylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate and tetraethylammonium perchlorate, and more preferably, the electrolyte is tetrabutylammonium tetrafluoroborate.
Preferably, the reaction solvent is one or two mixed solvents of acetonitrile, N-dimethylformamide, methanol, hexafluoroisopropanol, acetic acid and water, and more preferably the solvent is a mixed solvent of acetonitrile and acetic acid, and the volume ratio of the two is 9: 1.
Preferably, the electrodes comprise an anode electrode and a cathode electrode; the anode electrode is one of a graphite rod electrode, a platinum-plated electrode and a nickel electrode; the cathode electrode is one of a graphite rod electrode, a platinum-plated electrode and a nickel electrode, and more preferably, the electrode is a graphite rod anode and a nickel cathode.
Preferably, the constant current is 15 to 25mA, and more preferably the current is 20 mA. The specification of the adopted direct-current power supply is 5A and 30V;
preferably, the reaction time is 2 to 4 hours, more preferably 3 hours.
Preferably, the reaction temperature is 50 to 80 ℃, more preferably 60 ℃.
According to the invention, through inverse synthesis analysis, o-methylthio phenylboronic acid and phenylacetylene compounds are used as reaction substrates, boric acid groups are removed through electrochemical anodic oxidation to generate aryl radicals, the aryl radicals are added to the end of phenylacetylene to form vinyl radicals, and the vinyl radicals are attacked by methionine to remove methyl groups to form benzothiophene.
Compared with the prior art, the invention has the following advantages:
(1) according to the invention, aryl free radicals are excited by electrochemical oxidation, benzothiophene is constructed by the cascade reaction of the free radicals, electron transfer is realized by current, and no exogenous strong oxidant or transition metal catalyst is needed, so that the method is very suitable for drug synthesis.
(2) The method has the advantages of environmental protection, short reaction time, moderate reaction temperature, high reactant yield, good selectivity of target products and the like. Meanwhile, the method is simple to operate and low in cost, the yield of the product 2-phenyl-benzothiophene is as high as about 96%, and the method has a good industrial application prospect.
Drawings
FIG. 1 is a diagram showing the reaction mechanism of the present invention.
FIG. 2 is a nuclear magnetic hydrogen spectrum of the product of example 1 of the present invention.
FIG. 3 is a nuclear magnetic carbon spectrum of the product of example 1 of the present invention.
FIG. 4 is a nuclear magnetic hydrogen spectrum of a product of example 19 of the present invention.
FIG. 5 is a nuclear magnetic carbon spectrum of the product of example 19 of the present invention.
FIG. 6 is a nuclear magnetic hydrogen spectrum of the product of example 20 of the present invention.
FIG. 7 is a nuclear magnetic carbon spectrum of the product of example 20 of the present invention.
FIG. 8 is a nuclear magnetic hydrogen spectrum of a product of example 21 of the present invention.
FIG. 9 is a nuclear magnetic carbon spectrum of the product of example 21 of the present invention.
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.
Examples conversion was measured by HPLC and the data are shown in table 1, with the reaction substrate o-methylthiophenylboronic acid being 1 equivalent.
Example 1
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 96%.1H NMR(400MHz,CDCl3)δ7.86(d,J＝7.7Hz,1H),7.80(d,J＝7.1Hz,1H),7.75(d,J＝7.0Hz,2H),7.57(s,1H),7.49–7.42(m,2H),7.41–7.30(m,3H).13C NMR(100MHz,CDCl3)δ144.30,140.75,139.56,134.35,129.00,128.31,126.55,124.56,124.37,123.62,122.32,119.51.HRMS(ESI-TOF)m/z Calcd for C14H10S[M+H]+:211.0576,found:211.0568.
Example 2
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (0.5mmol, 51.03mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 81%.
Example 3
In a 50mL glass vial equipped with electrodes, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.5mmol, 153.08mg), the electrolyte tetrabutylammonium tetrafluoroborate (0.25mmol, 82.32mg) and the reaction solvent acetonitrile (9 mL)/acetic acid (1mL) were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 96%.
Example 4
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.5mmol, 164.64mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 94%.
Example 5
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate as an electrolyte (0.25mmol, 41.16mg), and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 83%.
Example 6
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate as an electrolyte (0.25mmol, 41.16mg), and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; a graphite rod electrode is used as an anode, a nickel electrode is used as a cathode and is connected with a direct current power supply, and a reaction bottle is placed in an oil bath at the temperature of 60 ℃ to be stirred and react for 3 hours under the constant current of 15 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 87%.
Example 7
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate as an electrolyte (0.25mmol, 41.16mg), and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode, connecting the graphite rod electrode and a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃, and stirring and reacting for 3 hours under the constant current of 25 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 93%.
Example 8
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate as an electrolyte (0.25mmol, 82.32mg), and acetonitrile (10mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 75%.
Example 9
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), an electrolyte tetrabutylammonium tetrafluoroborate (0.25mmol, 82.32mg), and a reaction solvent N, N-dimethylformamide (10mL) were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 61%.
Example 10
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/methanol (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 80%.
Example 11
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg), and acetonitrile (9 mL)/hexafluoroisopropanol (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 87%.
Example 12
In a 50mL glass vial equipped with electrodes, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), the electrolyte tetrabutylammonium tetrafluoroborate (0.25mmol, 82.32mg), and the reaction solvent acetonitrile (9 mL)/water (1mL) were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 91%.
Example 13
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 50 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 88%.
Example 14
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode, connecting the graphite rod electrode and a direct current power supply, placing a reaction bottle in an oil bath at 70 ℃, and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 95%.
Example 15
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode, connecting the graphite rod electrode and a direct current power supply, placing a reaction bottle in an oil bath at the temperature of 80 ℃, and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 93%.
TABLE 12 yield of phenyl-benzothiophenes
Example 16
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; a graphite rod electrode is used as an anode, a platinum electrode is used as a cathode and is connected with a direct current power supply, and a reaction bottle is placed in an oil bath at the temperature of 60 ℃ to be stirred and react for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 84%.
Example 17
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; a graphite rod electrode is used as an anode, a graphite rod electrode is used as a cathode and is connected with a direct current power supply, and a reaction bottle is placed in an oil bath at the temperature of 60 ℃ to be stirred and react for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 71%.
Example 18
In a 50mL glass vial equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), phenylacetylene (1.0mmol, 102.05mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; a nickel electrode is used as an anode, a graphite rod electrode is used as a cathode and is connected with a direct current power supply, and a reaction bottle is placed in an oil bath at the temperature of 60 ℃ to be stirred and react for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 63%.
Example 19
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), m-methylphenylacetylene (1.0mmol, 116.06mg), the electrolyte tetrabutylammonium tetrafluoroborate (0.25mmol, 82.32mg) and the reaction solvent acetonitrile (9 mL)/acetic acid (1mL) were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 95%.1H NMR(400MHz,CDCl3)δ7.84(d,J＝7.0Hz,1H),7.79(d,J＝8.3Hz,1H),7.55(d,J＝7.5Hz,3H),7.40–7.30(m,3H),7.18(d,J＝7.8Hz,1H),2.44(s,3H).13C NMR(100MHz,CDCl3)δ144.47,140.75,139.51,138.65,134.25,129.12,128.88,127.24,124.50,124.27,123.69,123.54,122.29,119.37,21.49.HRMS(ESI-TOF)m/z Calcd for C15H12S[M+H]+:225.0732,found:225.0725.
Example 20
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), p-ethylphenylacetylene (1.0mmol, 130.08mg), ammonium tetrabutyltetrafluoroborate as an electrolyte (0.25mmol, 82.32mg), and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with yield of 98%.1H NMR(400MHz,CDCl3)δ7.83(d,J＝7.3Hz,1H),7.77(d,J＝7.4Hz,1H),7.65(d,J＝8.1Hz,2H),7.52(s,1H),7.38–7.26(m,4H),2.70(q,J＝7.6Hz,2H),1.29(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3)δ144.67,144.46,140.82,139.40,131.78,128.48,126.51,124.47,124.14,123.44,122.26,118.90,28.66,15.51.HRMS(ESI-TOF)m/z Calcd for C16H14S[M+H]+:239.0889,found:239.0881.
Example 21
In a 50mL glass bottle equipped with an electrode, o-methylthiophenylboronic acid (0.5mmol,84.02mg), p-chlorophenylacetylene (1.0mmol, 136.01mg), ammonium tetrabutyltetrafluoroborate electrolyte (0.25mmol, 82.32mg) and acetonitrile (9 mL)/acetic acid (1mL) as a reaction solvent were added in this order; taking a graphite rod electrode as an anode, taking a nickel electrode as a cathode and connecting the cathode with a direct current power supply, placing a reaction bottle in an oil bath at 60 ℃ and stirring and reacting for 3 hours under the constant current of 20 mA; cooling to room temperature, washing with water, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, concentrating, and separating and purifying with silica gel column chromatography to obtain the target product 2-phenyl-benzothiophene with a yield of 92%.1H NMR(400MHz,CDCl3)δ7.85–7.80(m,1H),7.78(dd,J＝7.0,1.6Hz,1H),7.66–7.61(m,2H),7.52(s,1H),7.42–7.30(m,4H).13C NMR(100MHz,CDCl3)δ142.85,140.60,139.52,134.11,132.86,129.14,127.67,124.69,124.60,123.68,122.30,119.90.HRMS(ESI-TOF)m/z Calcd for C14H9ClS[M+H]+:245.0186,found:245.0180.
While the invention has been described with respect to a number of specific embodiments and methods, it will be appreciated by those skilled in the art that various modifications, additions and substitutions can be made without departing from the scope and spirit of the invention. All the components not specified in the present embodiment can be realized by the prior art.
Claims (8)
1. An electrochemical synthesis method of benzothiophene compounds is characterized by comprising the steps of adding o-methylthio phenylboronic acid, phenylacetylene compounds and electrolyte into a reaction solvent, inserting an electrode, and stirring for reaction under constant current to obtain benzothiophene compounds;
wherein R is selected from H, C1-C3 alkyl or halogen.
2. The method for electrochemically synthesizing benzothiophenes according to claim 1, wherein R is selected from the group consisting of H, CH3、CH2CH3Or Cl.
3. The electrochemical synthesis method of benzothiophenes compounds as claimed in claim 1, wherein the molar ratio of o-methylthiophenylboronic acid to phenylacetylene compound is 1: 1-1: 3; the molar ratio of the electrolyte to the o-methylthio phenylboronic acid is 1: 1-1: 4.
4. The electrochemical synthesis method of benzothiophenes compounds as claimed in claim 1, wherein said electrolyte is one or more of tetrabutylammonium fluoride, tetrabutylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate and tetraethylammonium perchlorate.
5. The electrochemical synthesis method of benzothiophenes, as claimed in claim 1, wherein said reaction solvent is one or more of acetonitrile, N-dimethylformamide, methanol, hexafluoroisopropanol, acetic acid and water.
6. The method for the electrochemical synthesis of benzothiophenes as claimed in claim 1, wherein said electrodes comprise an anode electrode and a cathode electrode; the anode electrode is one of a graphite rod electrode, a platinum-plated electrode and a nickel electrode; the cathode electrode is one of a graphite rod electrode, a platinized electrode and a nickel electrode.
7. The method for electrochemically synthesizing benzothiophenes compounds according to claim 1, wherein the constant current is 15 to 25 mA.
8. The electrochemical synthesis method of benzothiophenes, as claimed in claim 1, wherein said reaction time is 2-4 h; the reaction temperature is 50-80 ℃.
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